Leukemia, Hairy Cell

Key Features

Essentials of Diagnosis

• Pancytopenia

• Splenomegaly, often massive

• "Hairy" cells present on blood smear and especially in bone marrow biopsy

General Considerations

• Malignancy of hematopoietic stem cells differentiated as mature B-lymphocytes with "hairy" cytoplasmic projections

• V600E mutation in the BRAF gene

  • Recognized as the causal genetic event of hairy cell leukemia

  • Detectable in almost all cases at diagnosis and present at relapse

• Rare

Demographics

• Characteristically presents in middle-aged men

• Median age at presentation is 55 years

• Striking 5:1 male predominance

Clinical Findings

Symptoms and Signs

• Gradual onset of fatigue

• Symptoms related to markedly enlarged spleen

• Splenomegaly is almost invariably present and may be massive

• Increased susceptibility to infection

• Hepatomegaly in 50% of cases

• Lymphadenopathy uncommon

Differential Diagnosis

• Myelofibrosis

• Chronic lymphocytic leukemia

• Waldenström macroglobulinemia

• Non-Hodgkin lymphoma

• Aplastic anemia

• Other cause of bone marrow infiltration, eg, metastatic cancer, infection

Diagnosis

Laboratory Tests

• Complete blood count

  • Pancytopenia

  • Anemia nearly universal

  • Thrombocytopenia and neutropenia in 75% of patients

• Peripheral blood smear: "hairy cells," with numerous characteristic cytoplasmic projections, may be present in small numbers

• Hairy cells coexpress CD11c, CD20, CD22, CD25, CD103, and CD123 on immunophenotyping

Diagnostic Procedures

• Bone marrow aspirate: often inaspirable (dry tap)

• Bone marrow biopsy establishes diagnosis made by characteristic morphology

• Pathologic examination of spleen shows marked infiltration of red pulp with hairy cells (in contrast to usual predilection of lymphomas to involve white pulp)

Treatment

Medications

• Single course of pentostatin or cladribine

  • Treatment of choice

  • Median duration of response is over 8 years and patients who relapse a year or more from their initial therapy can be treated again with one of these agents

  • Treatment is associated with infectious complications and patients should be closely monitored

• Rituximab can be used in the relapsed setting either as a single agent or in combination with a nucleoside analog

• Vemurafenib, BRAF inhibitor

  • Exhibits ~100% overall response rate in patients with refractory/relapsed hairy cell leukemia, with 35–40% complete remissions

  • Median relapse-free survival is ~19 months in patients who achieved complete remission and 6 months in those who obtained a partial response

• Moxetumomab pasudotox

  • A recombinant CD22-targeting immunotoxin approved for patients with refractory disease

  • Has shown a durable complete response rate of 31% in the pivotal trial

  • However, it can be associated with capillary leak and hemolytic-uremic syndrome attributable to the diphtheria toxin moiety

• See Table 39–3